精神分裂癥是大腦發(fā)育異常導(dǎo)致的嚴(yán)重精神疾病,，科學(xué)家們正在對此開展基因?qū)W研究，以期找到精神分裂癥的致病基因,。2008年3月的愛思唯爾期刊《生物精神病學(xué)》（Biological Psychiatry）在顯著位置刊登了一篇關(guān)于精神分裂癥致病基因新發(fā)現(xiàn)的研究論文,。
一項(xiàng)基因圖譜研究發(fā)現(xiàn)，一個名為“MEGF10”的基因可能與精神分裂癥的病理過程有關(guān),。此前的研究發(fā)現(xiàn),，MEGF10基因會影響人體表皮生長。在最新研究中,，弗吉尼亞聯(lián)邦大學(xué)醫(yī)學(xué)院助理教授Xiangning Chen和同事直接對比分析了精神分裂癥患者與普通人MEGF10基因的不同,。他們發(fā)現(xiàn)，在家族基因研究和病例-對照基因研究中,，MEGF10基因決定了精神分裂癥的遺傳風(fēng)險,。此外，研究人員通過尸體腦組織的解剖對比發(fā)現(xiàn),，MEGF10基因?qū)δX部發(fā)育影響很大,。
Chen說：“該文章的重要性在于，它表明了直接控制細(xì)胞凋亡的MEGF10基因與精神分裂癥之間存在某種聯(lián)系,?？茖W(xué)家們一致懷疑是腦細(xì)胞凋亡紊亂引起了精神分裂癥，卻一直缺乏直接證據(jù),。細(xì)胞凋亡是人類和其它復(fù)雜生物體細(xì)胞程序性死亡的重要生物學(xué)過程,，該過程的異常會導(dǎo)致很多疾病。”
《生物精神病學(xué)》雜志的編輯,、耶魯大學(xué)醫(yī)學(xué)院的John H. Krystal博士評論說：“文章懷疑精神分裂癥與MEGF10基因有關(guān),，而此前的研究發(fā)現(xiàn)MEGF10基因影響人體表皮生長?？梢詮膬蓚€方面來理解,。一是在人類胚胎發(fā)育早期，神經(jīng)細(xì)胞與皮膚細(xì)胞都起源于同一種類型的原胞,。二是精神分裂癥患者的表皮發(fā)育,，例如指紋，與普通人相比會表現(xiàn)出異常,。”
該論文表明,，有必要進(jìn)一步深入研究MEGF10基因，探索該基因如何影響大腦發(fā)育和如何改進(jìn)精神分裂癥治療方法,。（科學(xué)網(wǎng) 荔濤/編譯）
生物谷推薦原始出處：
（Biological Psychiatry）,，doi:10.1016/j.biopsych.2007.11.003 ，Xiangning Chen, Kenneth S. Kendler
MEGF10 Association with Schizophrenia
Xiangning Chena, , , Xu Wanga, Qi Chena, Vernell Williamsona, Edwin van den Oordb, Brion S. Mahera, F. Anthony O’Neillc, Dermot Walshd and Kenneth S. Kendlera
aDepartment of Psychiatry, the Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA
bDepartment of Pharmacy and Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, VA
cDepartment of Psychiatry, The Queens University, Belfast, Northern Ireland
dThe Health Research Board, Dublin, Ireland.
Received 23 August 2007; revised 7 November 2007; accepted 8 November 2007. Available online 7 January 2008.
Background
The 5q21–31 region has been implicated as harboring risk genes for schizophrenia in many linkage studies. In our previous report of stepwise fine mapping of this region, the MEGF10 gene was one of the genes showing consistent associations in our screening subsample. In this study, we carried out independent replication and expression studies of the MEGF10 gene.
Methods
Association studies with 8 SNPs in the MEGF10 gene were performed in the Irish case-control study of schizophrenia (ICCSS) sample (652 case and 617 control subjects). The expression of MEGF10 was also compared between healthy control subjects and schizophrenia patients using postmortem brain cDNA libraries.
Results
In the ICCSS sample, associations with the disease were found in the same risk alleles and haplotypes as that observed in our fine-mapping studies. The major allele (A) of rs27388 was overrepresented in affected individuals (p = .0169), which remained significant after correction for multiple testing. In expression studies, MEGF10 had higher expression levels in the affected than the unaffected (p = .015). Schizophrenia patients with a 1/1 genotype at rs27388 had higher expressions than those patients with 1/2 and 2/2 genotypes (p = .0008).
Conclusions
Evidence from both association and expression studies suggests that MEGF10 is likely associated with schizophrenia. The major allele and 1/1 genotype at rs27388 impose higher risks for the disease.
